PROJECT SUMMARY/ABSTRACT My long-term career goal is to be an independent investigator who develops effective obesity treatments and matches these treatments to patients' characteristics. Through my training in clinical psychology, I gained skills in the development and delivery of behavioral treatments (BTs) for obesity and in conducting randomized controlled trials (RCTs) to test their efficacy. As a postdoctoral fellow, I was then introduced to obesity pharmacotherapy, but still have limited experience in this area. In order to successfully develop a career in precision medicine for obesity, I will need additional training in behavioral, biological, and pharmacological influences on body weight. The proposed K23 award will allow me to devote 95% effort to filling critical gaps in my training and to conducting research that will prepare me to be an independent investigator in obesity treatment. My training plan will prepare me for an independent research career by increasing my knowledge in three key areas: 1) behavioral phenotypes associated with obesity and methods for their objective measurement; 2) neuroendocrine mechanisms of energy balance regulation that may impact weight loss; and 3) the use of pharmacologic agents to improve weight loss. I will accomplish these objectives by receiving guidance from mentors, engaging in hands-on research training, and completing relevant coursework and seminars. My research project will complement these training goals by examining behavioral phenotypes and neuroendocrine biomarkers as predictors of early weight loss and by testing whether medication enhances weight loss in patients with a suboptimal early response to BT alone. Participants will complete an initial assessment of behavioral and biological characteristics, followed by 4 weeks of BT. Those who lose < 2.0% of initial weight during the run-in will then be randomly assigned to an additional 24 weeks of: 1) BT plus placebo; or 2) BT plus medication (phentermine 15.0mg). I believe that low satiety will predict poor early weight loss with BT and that pharmacotherapy will enhance 24-week weight loss for patients with suboptimal response to BT. This project could shape best practice recommendations for obesity treatment and ultimately result in algorithms for matching treatments to patient characteristics. The environment at the Center for Weight and Eating Disorders at the University of Pennsylvania is well-equipped with staff, resources, and infrastructure to support the proposed project. I coursework, will also access state-of-the-art facilities, and seminars at Penn to complete my research and training goals.My mentorship team will be led by Dr. Thomas Wadden (Professor of Psychology) and includes training from Dr. Tanja Kral (Associate Professor of Nursing) in behavioral phenotypes of obesity and Dr. Matthew Hayes (Associate Professor of Nutritional Neuroscience)in mechanisms of energy balance.This comprehensive, interdisciplinary mentored approach will allow me to acquire knowledge in areas essential to my career goals, implement the proposed research plan, and develop a successful R01 application prior to the end of the K23 award.